The basic aim of this grant proposal is to use laboratory techniques, primarily immunologic, to explore diagnostic and therapeutic approaches to human allergic disorders. Obviously, our objective is to improve these techniques and to thereby improve the clinical care of allergic disorders. A major tool in these studies remains the in vitro model of histamine release from human leukocytes. With this system we can assess the sensitivity of patients to various allergens, measure changes in sensitivity induced by immunotherapy, and assess quantitatively the biologic activity of various allergenic preparations. Over the previous grant period we have developed other tools, particularly RAST technology to measure IgE antibodies and double antibody radioimmunoassays to measure IgG antibodies. With these we will study the changes in these antibody levels during the natural course of allergic diseases and after immunotherapy. Finally, the ability to measure total IgE levels and absolute IgE antibody levels will enable us to explore in depth the interaction between serum and cell-bound IgE. These laboratory tools will be used to attack two main clinical areas. The first is a continuation of our studies of immunotherapy for pollinosis, concentrating primarily on new modes of treating ragweed and grass hay fever. This includes allergoid immunization and new treatment regimens (i.e., "rush desensitization"). We are also beginning studies of immunotherapy for pollen-induced seasonal asthma. The other major clinical area of interest is Hymenoptera sensitivity. In this instance we will study the utility of Hymenoptera venoms in the diagnosis of this disease and in therapeutic trials. We aim also to characterize the major allergens in the venoms of the vespid species so that standardization of the venoms can be established and to allow definitive RAST and IgG antibody measurements in sensitive patients. In each instance these studies are well underway, funded during the previous grant period, and the results appear to be promising in our overall goal of using basic immunologic knowledge to advance the treatment of allergic disorders.